Objective:To study the regulatory effect of somatostatin analogue octreotide on human gastric cancer cell line SGC7901 and to explore the corresponding mechanisms.Methods:Moderately differentiated human gastric carcinoma SGC-7901 cells were treated with octreotide in vitro.SGC-7901 cells treated with 5-FU were the positve controls and human fibroblasts were the normal controls.MTT assay was used to observe the inhibitory effect of octreotide on human gastric carcinoma cells and human fibroblasts.We observed the apoptosis through fluorescent microscope.The influence of octreotide on cell cycle distribution and the apoptosis rate of human gastric carcinoma cell were analyzed with FCM.Radiommunoassay was employed to determine the changes in IGF-1 levels in cell culture fluid.Results:Octretide can not inhibit the growth of gastric cells at low concentration(50ug/L).With the increase of octretide concentration,the inhibitory effect increased gradually,in a dose-dependent manner.Octretide had an evident inhibitory effect on human fibroblasts(P>0.05).There was no difference in the inhibition of SGC-7901 cell growth between octretide (500ug/L)and 5-FU(50mg/L)(P>0.05).At 48 hours after treatment with octretide(1 mg/L),the morphological changes of apoptosis were seen under fluorescent microscope.At 48 hours after treatment with octretide (500ug/L),most cells were blocked at G_0/G_1 phase(72.07±2.40).The percentage of cells at S phase was decreased signiflcantly(14.99±1.42).The proliferation of cells was inhibited and the apoptosis rate was increased(21.40±2.71).With octretide treatment at different concentrations.IGF-1 level in cell culture fluid was significantly lower than that in the control group(P<0.01),indicating that octretide down-regulated IGF-1 level in the call culture system.Conclusion:Octroetide can inhibit the growth of gastric carcinoma cells in vitro,with no significant inhibition on the growth of non-target cells.Octroetide can induce gastric cancer cell stagnation at G_0/G_1 phase and apoptosis,inhibiting the proliferation directly.Octroetide can also inhibit the secretion of IGF and restrain tumor cell growth indirectly.

Aging ; Humans ; Presbycusis ; genetics

Objective To analyze the levels and speciation of arsenic metabolites in urine of rats treated with sodium arsenite and sodium arsenate in order to investigate the different aspects of metabolism between sodium arsenite and sodium arsenate,thus to understand further the basic data about relationship between it's metabolism and mechanism of toxicity. Methods Seventy Wistar rats,weighting 80-120 g,were divided into 7 groups of 10 each,such as normal control group,high,middle and low sodium arsenite group and high,middle and low sodium arsenate group. After the animals were fed for one month,the urine was collected by metabolic cage in 12 hours. Applying the high efficiency liquid chromatography and hydride genesis atomic fluorescence spectroscopy (HPLC-HGAFS),the levels and speciation of arsenic metabolites were determined in urine of rats. Meanwhile,the recovery rate of dimethyl arsinic acid(DMA) would be determined to estimate the degree of accuracy of results. Results The levels of iAs~(3+),iAs~(5+) and DMA in middle sodium arsenite group[(121.66±1.26),(10.26±2.68),(200.91±0.56) μg/L]were higher than the high sodium arsenite group[(113.20±0.75),(5.16±1.32),(147.70±μ0.77)μg/L,all P < 0.05]and low sodium arsenite group[(79.35±2.12),(5.13±2.25),(56.35±1.23)μg/L,all P < 0.05]. The levels of iAs~(3+) and DMA in middle sodium arsenate group[(315.81±1.69),(245.12±1.18)μg/L]were higher than the high sodium arsenate group[(85.03±0.56),(110.34±1.04)μg/L,all P< 0.05]and low sodium arsenate group[(22.97±2.67),(15.75±2.15)μg/L,all P < 0.05]. Compared with sodium arsenate group,the levels of iAs~(3+) and DMA in high and low sodium arsenite group were higher(all P < 0.05) ; and the levels of iAs~(3+) and DMA in middle sodium arsenite group were lower(all P < 0.05). Meanwhile,the average urinary recovery rate of DMA of rats in different sodium arsenite group were 94.80%-102.70%,and the average urinary recovery rate of DMA of rats in different sodium arsenate group were 95.33%-108.40%. Conclusion The speciation and levels of arsenic are influenced by the external exposure dose,and some distinction appeared in the metabolism and metabolic path between sodium arsenite and sodium arsenate in urine in vivo.

Objective To evaluate the effects of TIMP-1 and Ang-1 gene-modified BMSCs transplantation on the left ventricular function of rats with myocardial infarction.Methods The rat BMSCs were.transfected with eukaryotic expression plasmid encoding TIMP-1 or/and Ang-1 gene by liposome.Acute myocardial infarction was made in male rats by ligation of the left anterior descending (LAD) coronary artery.BMSCs carrying TIMP-1 or/and Ang-1 gene were injected into the ischemic myocardium after LAD ligatior.Four weeks after the administration,cardiac function was assessed by echocardiography and the hearts were harvested and sectioned for immunohistochemistry to examine the apoptosis,the collagen content and angiogenesis density.Results TIMP-1 and Ang-1 genemodified BMSCs transplantation significantly improved the cardiac function,myocardial apoptosis was alleviated,collagen content decreased and the angiogenesis density in border-zone was increased significantly (P＜0.05).Conclusions The results suggest that the combination of TIMP-1 and Ang-1-gene modified BMSCs transplantation can improve the cardiac function of rats with myocardial infarction.The increase of the blood supply,the alleviation of myocardial apoptosis and ventricle remolding after myocardial infarction possibly play important roles in the mechanism.

AIM: To investigate the crosstalk between angiotensin Ⅱ (AngⅡ)-mediated and platelet-derived growth factor (PDGF)-mediated signal transduction in vascular smooth muscle proliferation.METHODS: A model of renal hypertension was made by two kidney/one-clip operation. Level of PDGF receptor ? subunit of aorta was measured by Western Blot analysis. The effect of Ang Ⅱ on PDGF receptor ? subunit expression was investigated in culture rat aortic vascular smooth muscle cells (VSMC).RESULTS: Systolic blood pressure obviously increased at 8th week after operation, whereas the level of PDGF receptor ? subunit of aorta significantly increased by 126.6% ( P

AIM: To investigate the changes of G?q/11 and phospholipase C(PLC) of the aorta and to evaluate the role of signal transduction pathway mediated by G?q/11 in the pathogenesis of spontaneous hypertension. METHODS: Blood pressure was measured by intubation of carotid, and the level of plasma angiotension Ⅱ was measured by radioimmunoassay. In addition, G?q/11 and PLC contents in aorta were determined by Western blot analysis. RESULTS: Arterial blood pressure was not changed in 4-week-old spontaneously hypertensive rats(SHR), but it was increased markedly in 12-week-old SHR. The G?q/11 expression of aorta in 4-week-old SHR was increased by 69 2%( P

AIM: To investigate the crosstalk between angiotensin Ⅱ (AngⅡ)-mediated and platelet-derived growth factor (PDGF)-mediated signal transduction in vascular smooth muscle proliferation.METHODS: A model of renal hypertension was made by two kidney/one-clip operation. Level of PDGF receptor β subunit of aorta was measured by Western Blot analysis. The effect of Ang Ⅱ on PDGF receptor β subunit expression was investigated in culture rat aortic vascular smooth muscle cells (VSMC).RESULTS: Systolic blood pressure obviously increased at 8th week after operation, whereas the level of PDGF receptor β subunit of aorta significantly increased by 126.6% (P＜0.05) in 2K1C rats compared with control group. The expression of PDGF receptor β subunit in cultured VSMC stimulated by AngⅡ was higher than that of control by 192.74%(P＜0.01). The effect of AngⅡ was inhibited remarkably by pretreated with losartan, a kind of specific AngⅡ receptor 1 (AT1) subtype antagonist and U73122, a kind of phospholipase C inhibitor. The effect was partly blocked by PD98059, which inhibit the activity of mitogen-activated, ERK-activating kinase (MEK).CONCLUSION: AngⅡ-induced PDGF receptor β subunit expression is regulated by the AT1 and its downstream signal molecule-PLC and ERK, might participate in the intracellular signal transduction pathway.

Aim To study the effects of aspirin on increasing the atherosclerotic plaque stability and its possible mechanisms.Methods The hyperlipidemic atherosclerotic model was generated in male New Zealand rabbits given high fat diet and endothelial abrasion of abdominal aorta.These rabbits were then treated with aspirin 5～20 mg?kg-1 for 4 weeks.At experimental end,the plaques were evoked into rupture by injection of Russell's viper venom and histamine.Areas of thrombosis on atherosclerotic aorta were determined by image analysis,morphologic character of plaque rupture was examined by light microscope,the protein expression of macrophages was detected by immunohistochemistry,and the mRNA expression of COX-2 and MMP-2 was determined by hybridization in situ,respectively.Results Aspirin at doses of 5～10 mg?kg-1 was able to inhibit thrombosis on atherosclerotic plaque(P

0.05). CONCLUSION: There are no significant differences in cell characteristics and transplantation outcome using OB-OEC and OM-OEC transplantation for repairing neurological function.

Objective To observe the effect of intra-articular injection of dehydroepiandrosterone (DHEA)on the experimental osteoarthritis in rabbits and study the mechanism.Methods Forty rabbits un derwent unilateral anterior cruciate ligament transection(ACLT)and then divided into two groups randomly. 100?mol/L DHEA resolved in the dimethylsulphoxide were injected into the knees of experimental rabbits 4 weeks after transection,once a week for five weeks.Rabbits in the control group were treated under the same schedule using dimethylsulphoxide.All rabbits were killed 9 weeks after ACLT and the knee joints were evalu- ated by gross morphology and histology.The mRNA expression of metalloproteinases-3(MMP-3),tissue in- hibitor of metalloproteinases-1(TIMP-1)and interleukin-lbeta(IL-1?)in the cartilage and synovium was analyzed using reverse transcription polymerase chain reaction(RT-PCR).Results Gross morphologic in- spection and histological evaluation showed that the extent and grade of cartilage and synovium damage in the experimental group were less severe than the control group.The mRNA expression of MMP-3 in cartilage and synovium decreased significantly in the experimental group(both P＜0.05).The mRNA expression of TIMP-1 in cartilage and synovium increased significantly in the experimental group compared with that in the control group(both P＜0.05).No significant difference of IL-1?mRNA expression in cartilage was found between the experimental and the control groups(P＞0.05).The mRNA expression of IL-1?in the synovium was signifi- cantly suppressed in the experimental group compared with that in the control group(P＜0.01).Conclusion DHEA protects against cartilage degradation,alleviates synovium inflammation and inhibits the progression of osteoarthritis in the experimental model.Down-regulation of MMP-3 and up-regulation of TIMP-1 in cartilage and synovium and IL-1?in the synovium may be the mechanism of the protective effect of DHEA on os- teoarthritis.